Aaron L. Berkowitz

A Developmental Functional MRI Study of Spatial Working Memory

Functional magnetic resonance imaging (fMRI) was used to examine patterns of cortical activity in children during performance of a spatial working memory task. Six children (8-10 years) and six adults (19-26 years) searched a linear array of four boxes for the appearance of a dot. In the visual blocks, participants made no response. In the motor blocks, participants were instructed to indicate the location of the dot on each trial using a button-press response. In the working memory blocks, participants were instructed to indicate at which location the dot had appeared 1 or 2 trials previously. Both children and adults showed activity in the left precentral and postcentral gyri, as well as the right cerebellum for the motor condition as compared to the visual condition. Comparison of the memory and motor conditions revealed reliable activity in the right superior frontal gyrus (BA 8), right dorsolateral prefrontal cortex (BA 10/46), right superior parietal cortex, and bilateral inferior parietal cortex for both adults and children. These results suggest that spatial working memory tasks activate very similar cortical regions for school-age children and adults. The findings differ from previous imaging studies of nonspatial working memory tasks in that the prefrontal activations observed in the current work tend to be more dorsal. Results are discussed in light of the significant behavioral performance differences observed between child and adult participants.

Does my dizzy patient have a stroke? A systematic review of bedside diagnosis in acute vestibular syndrome

Dizziness is the third most common major medical symptom reported in general medical clinics[1][1] and accounts for about 3%–5% of visits across care settings.[2][2] In the United States, this translates to 10 million ambulatory visits per year because of dizziness,[3][3] with roughly 25% of these

Sensitivity of prefrontal cortex to changes in target probability: A functional MRI study

Electrophysiological studies suggest sensitivity of the prefrontal cortex to changes in the probability of an event. The purpose of this study was to determine if subregions of the prefrontal cortex respond differentially to changes in target probabilities using functional magnetic resonance imaging (fMRI). Ten right‐handed adults were scanned using a gradient‐echo, echo planar imaging sequence during performance of an oddball paradigm. Subjects were instructed to respond to any letter but “X”. The frequency of targets (i.e., any letter but X) varied across trials. The results showed that dorsal prefrontal regions were active during infrequent events and ventral prefrontal regions were active during frequent events. Further, we observed an inverse relation between the dorsal and ventral prefrontal regions such that when activity in dorsal prefrontal regions increased, activity in ventral prefrontal regions decreased, and vice versa. This finding may index competing cognitive processes or capacity limitations. Most importantly, these findings taken as a whole suggest that any simple theory of prefrontal cortex function must take into account the sensitivity of this region to changes in target probability. Hum. Brain Mapping 13:26–33, 2001.

Generation of novel motor sequences: The neural correlates of musical improvisation

While some motor behavior is instinctive and stereotyped or learned and re-executed, much action is a spontaneous response to a novel set of environmental conditions. The neural correlates of both pre-learned and cued motor sequences have been previously studied, but novel motor behavior has thus far not been examined through brain imaging. In this paper, we report a study of musical improvisation in trained pianists with functional magnetic resonance imaging (fMRI), using improvisation as a case study of novel action generation. We demonstrate that both rhythmic (temporal) and melodic (ordinal) motor sequence creation modulate activity in a network of brain regions comprised of the dorsal premotor cortex, the rostral cingulate zone of the anterior cingulate cortex, and the inferior frontal gyrus. These findings are consistent with a role for the dorsal premotor cortex in movement coordination, the rostral cingulate zone in voluntary selection, and the inferior frontal gyrus in sequence generation. Thus, the invention of novel motor sequences in musical improvisation recruits a network of brain regions coordinated to generate possible sequences, select among them, and execute the decided-upon sequence.

Glioproliferative Lesion of the Spinal Cord as a Complication of “Stem-Cell Tourism”

A primitive neoplasm composed predominantly of nonhost cells was detected in the thoracic spinal cord and thecal sac of a 66-year-old man who had received experimental stem-cell treatment from commercial clinics.

Antibiotic-associated encephalopathy.

Delirium is a common and costly complication of hospitalization. Although medications are a known cause of delirium, antibiotics are an underrecognized class of medications associated with delirium. In this article, we comprehensively review the clinical, radiologic, and electrophysiologic features of antibiotic-associated encephalopathy (AAE). AAE can be divided into 3 unique clinical phenotypes: encephalopathy commonly accompanied by seizures or myoclonus arising within days after antibiotic administration (caused by cephalosporins and penicillin); encephalopathy characterized by psychosis arising within days of antibiotic administration (caused by quinolones, macrolides, and procaine penicillin); and encephalopathy accompanied by cerebellar signs and MRI abnormalities emerging weeks after initiation of antibiotics (caused by metronidazole). We correlate these 3 clinical phenotypes with underlying pathophysiologic mechanisms of antibiotic neurotoxicity. Familiarity with these types of antibiotic toxicity can improve timely diagnosis of AAE and prompt antibiotic discontinuation, reducing the time patients spend in the delirious state.

The neurology of Sjogren's syndrome and the rheumatology of peripheral neuropathy and myelitis.

Neurological symptoms occur in approximately 20% of patients with Sjögrens syndrome, and may be the presenting manifestations of the disease. Here, we review several neurological conditions that can occur in Sjögrens syndrome: sensory ganglionopathy, painful small fibre neuropathy, and transverse myelitis (independently or as part of neuromyelitis optica). We present the symptoms, signs, differential diagnoses, recommended diagnostic evaluation, and treatment of each of these, highlighting the features that should alert neurologists to consider Sjögrens syndrome.

Zika virus–associated Guillain-Barré syndrome variant in Haiti

Zika virus is a single-stranded RNA virus (genus Flavivirus) transmitted by the Aedes mosquito and through sexual contact with infected individuals.1,2 Zika virus infection may be asymptomatic or may cause fever, rash, joint pain, conjunctivitis, myalgias, and headache.1 Initially endemic to Africa and Asia, outbreaks in the Pacific Islands occurred in 2007 and 2013, and Central America, South America, and the Caribbean islands are currently in the midst of an epidemic. In both prior and current outbreaks of Zika,1 an increased incidence of Guillain-Barré syndrome (GBS) has been reported.

Worldwide reported use of IV tissue plasminogen activator for acute ischemic stroke

Background and Purpose Intravenous tissue plasminogen activator is the most effective treatment for acute ischemic stroke, and its use may therefore serve as an indicator of the available level of acute stroke care. The greatest burden of stroke is in low- and middle-income countries, but the extent to which intravenous tissue plasminogen activator is used in these countries is unreported. Summary of Review A systematic review was performed searching each country name AND ‘stroke’ OR ‘tissue plasminogen activator’ OR ‘thrombolysis’ using PubMed, Embase, Global Health, African Index Medicus, and abstracts published in the International Journal of Stroke (Jan. 1, 1996–Oct. 1, 2012). The reported use of intravenous tissue plasminogen activator was then analyzed according to country-level income status, total expenditure on health per capita, and mortality and disability-adjusted life years due to stroke. There were 118 780 citations reviewed. Of 214 countries and independent territories, 64 (30%) reported use of intravenous tissue plasminogen activator for acute ischemic stroke in the medical literature: 3% (1/36) low-income, 19% (10/54) lower-middle-income, 33% (18/54) upper-middle-income, and 50% (35/70) high-income-countries (test for trend, P < 0·001). When considering country-level determinants of reported intravenous tissue plasminogen activator use for acute ischemic stroke, total healthcare expenditure per capita (odds ratio 3·3 per 1000 international dollar increase, 95% confidence interval 1·4–9·9, P = 0·02) and reported mortality rate from cerebrovascular disease (odds ratio 1·02, 95% confidence interval 0·99–1·06, P = 0·02) were significant, but reported disability-adjusted life years from cerebrovascular diseases and gross national income per capita were not (P > 0·05). Of the 10 countries with the highest disability-adjusted life years due to stroke, only one reported intravenous tissue plasminogen activator use. Conclusions By reported use, intravenous tissue plasminogen activator for acute ischemic stroke is available to some patients in approximately one-third of countries. Access to advanced acute stroke care is most limited where the greatest burden of cerebrovascular disease is reported.

Neurologic manifestations of the neglected tropical diseases

BACKGROUND The World Health Organization has identified 17 neglected tropical diseases (NTDs) that disproportionately affect the worlds poorest populations. The neurologic aspects of many of these NTDs have received relatively little attention. METHODS A review was performed in PubMed (MedLine) for each NTD by disease name, name of its causative organism, and neurology, neurosurgery, neurologist, brain, spinal cord, peripheral nerve, muscle, nervous system, encephalitis, meningitis, encephalopathy, stroke, neuropathy, and myopathy (1968-Sept. 2013). The Oxford Center for Evidence-based Medicine guidelines were used to determine the level of evidence of neurological involvement and treatment based on the reports identified. RESULTS Neurologic manifestations were reported for all NTDs except yaws. Neurologic involvement was described in systematic reviews for four NTDs (Chagas disease, echinococcosis, rabies, cysticercosis) (levels 2a-3a), retrospective cohort studies for six (dengue, human African trypanosomiasis, leishmaniasis, leprosy, onchocerciasis, schistosomiasis) (levels 2b-3b), case series for one (foodborne trematodiasis) (level 4), and case reports for five (Buruli ulcer, dracunculiasis, filariasis, soil-transmitted helminthes, and trachoma). Level 1 evidence for treatment of neurologic manifestations of NTDs was found for human African trypanosomiasis, leprosy, and cysticercosis and level 2 evidence exists for treatment of neurologic involvement in Chagas disease. For the remaining NTDs, treatment of neurologic complications is described in case series and case reports only. CONCLUSIONS Neurologic manifestations of NTDs cause significant morbidity and mortality, although limited evidence exists on how best to treat these neurologic complications. Increased awareness of neurologic manifestations of the NTDs can increase their early identification and treatment, contributing to ongoing elimination and eradication campaigns.